tbuckley/cabot-search huggingface dataset:
Hypofractionated radiotherapy compared with conventionally fractionated radiotherapy to treat initial distant metastases in nasopharyngeal carcinoma: A multicenter, prospective, randomized, phase II trial.
Authors: Wei Jiang, Jian Liu, Bin Zhang, Yixin Su, Guanjie Qin, XiangYun Kong, Yunyan Mo, Rongjun Zhang
Journal: Journal of Clinical Oncology (2023)

e18019 Background: To investigate the safety and efficacy of hypofractionated plus chemotherapy in patients with initially distant metastatic nasopharyngeal carcinoma (mNPC). Methods: Between May 2014 and June 2020, 35 patients initially diagnosed with mNPC were enrolled on prospective trial. The enrolled patients were assigned randomly to receive either hypofractionated plus chemotherapy (HFRT) or conventionally fractionated radiotherapy plus chemotherapy (CFRT). 60 Gy over 25 fractions was administered to the HFRT group (n = 17) and 69.96 Gy over 33 fractions was administered to the CFRT group (n = 18), both groups five times each week. Progression free survival (PFS) comprised the primary endpoint. Overall survival (OS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS), and acute and late toxicity comprised the secondary endpoints. Results: Twenty-eight patients (seven were excluded) were enrolled. The 2-year PFS was 33.3% (HFRT group) versus 30.0% (CFRT group) (stratified hazard ratio (HR):1.09; 95% confidence interval (CI): 0.45–2.65, P = .843). The 2-year OS was 66.7% (HFRT group) versus 62.5% (CFRT group) (stratified HR, 0.88; 95% CI; 0.31–2.51, P= .806). All patients experienced acute grade 1 or 2, skin toxicity, oral mucositis, dysphagia, dry mouth, but no acute grade 3 or 4 toxicities. All patients had grade 1 late xerostomia. Two patients experienced hearing loss (one grade 1 and one grade 3). One patient developed mucosal necrosis. Conclusions: The two groups had similar outcomes. Improving the balance between severe late toxicities and local control by appropriately reducing the total dose but increasing the fractionated dose has marked clinical significance for patients with initially diagnosed mNPC. The trial has been registered with clinicaltrials.gov (NCT03598218). Clinical trial information: NCT03598218 . [Table: see text]
Responses in patients with AML and treated with entospletinib monotherapy.
Authors: Tara L. Lin, Richard E. Cutler, Elizabeth Olek, Luis A. Carvajal, Jorge F. DiMartino, Alison R. Walker
Journal: Journal of Clinical Oncology (2023)

e19010 Background: AML is a disease defined by the acquisition of genetic lesions in normal hematopoietic stem cells and progenitors resulting in poorly differentiated and highly proliferative leukemic blasts. Spleen tyrosine kinase (SYK) is a nonreceptor tyrosine kinase that maintains de-differentiation and leukemogenesis. MLL rearrangements (MLL-r) occur in up to 10% of adult AML and are associated with upregulated expression of the transcription factors HOXA9 and MEIS1 and worse clinical outcomes. Entospletinib (ENTO), an oral, selective inhibitor of SYK, has been studied in clinical trials for unselected AML patients as well as MLL-r patients. ENTO plus standard induction chemotherapy in front line had a 76% (13/17) composite complete response (CR) in AML patients with high HOXA9 and MEIS1. We have 3 patients that achieved CRs with ENTO monotherapy; one patient achieved CR to 14 days of ENTO monotherapy prior to initiation of chemotherapy; 2 patients with relapsed/refractory AML with MLL-r treated with ENTO monotherapy achieved CRs. Methods: This was part of an international multicenter phase Ib/II study (NCT02343939) which evaluated the efficacy, safety, and tolerability of ENTO in subjects with AML. During dose escalation, ENTO was administered in combination with induction chemotherapy (Group A) or with a hypomethylating agent (Group B). ENTO was administered as monotherapy for R/R AML in Group C. This report includes one patient from group A (newly diagnosed AML, MLL-r, 14-day monotherapy lead-in with ENTO) and two patients from group C monotherapy (relapsed/refractory AML, MLL-r). Results: Three patients receiving ENTO monotherapy had CRs. 18-year-old male from group A, that was MLL-r, NPM1-mutant (-). Patient treated at 400 mg PO, BID, achieved a cytogenetic CR with incomplete count recovery after cycle 0 (before chemotherapy); the patient continued study with induction chemotherapy and ultimately received ASCT in CR. Two additional patients in group C (with multiple therapies), both at 400 mg bid: (i) 37-year-old male, MLL-r, NPM1(-), was on study for 28 days, achieved CR; (ii) 28-year-old female, MLL-r, NPM1(-) on study for 60 days, achieved CR, both proceeded to SCT. Conclusions: Based on the results from these three patients, the clinical activity of SYK inhibition should be explored further in AML. We are testing Lanraplenib, a next-generation SYK inhibitor with enhanced selectivity, and more favorable pharmacologic properties in combination in genetically defined subsets of AML (NCT05028751). Clinical trial information: NCT02343939 .
Combinatorial immune biomarkers of efficacy on buparlisib and paclitaxel in patients with SCCHN: BERIL-1 sub-analysis.
Authors: Denis Soulieres, Justin Lucas, Sherry Xu, Sunny Lu, Kevin Dreyer, Nanhai He, Tom Tang, Lars E Birgerson, Lisa F. Licitra, Sandrine Faivre
Journal: Journal of Clinical Oncology (2023)

e18030 Background: Previous analysis of the BERIL-1 Phase 2 clinical trial (Soulieres et al, CCR, 2018), evaluating the efficacy of Buparlisib + Paclitaxel, was one of the largest genomic landscape analyses to date in metastatic SCCHN. With the recent approval of PD-1 in this indication, we sought to expand the analysis, focusing on combinatorial biomarkers of immune infiltration in addition to specific genomic alterations. The goal is to evaluate hierarchically prognostic and predictive biomarkers to select predefined analysis in the current Phase 3 clinical trial, BURAN (NCT04338399) post immune modulatory therapy. Methods: The results of this analysis focused on combination of genomic alterations in both tumor and plasma samples. Alterations found in tumor versus plasma revealed over 50 differentially altered genes. Combination of these sample types is more comprehensive of the patients’ true mutational and copy number status; no significant differences in alteration frequency between treatment and placebo treatment arms were identified. We evaluated correlations between select biomarkers and improvement in efficacy end points of Progression Free Survival (PFS) and Overall Survival (OS) between the treatment and control arms and within the treatment arm. Results: The most frequently altered genes were, TP53 (49%), NOTCH1 (21%), PIK3CA (19%), FAT1 (15%), and CDKN2A (13%). Previous analysis demonstrated that TP53 mutations as well as high immune infiltration (&gt; 10% intratumoral or stromal TILs) showed improvement in PFS &amp; OS. Further improvement to OS was observed in subjects with high immune infiltration and TP53 (p = .031, HR = 0.52), PIK3CA (p = .005, HR = 0.34), NOTCH1(p = .046, HR = 0.13) or FAT1(p = .007; HR = 0.28) alterations when compared to non-altered subjects in the treatment arm. Further improvement to PFS was observed in subjects with high immune infiltration and TP53(p = .031, HR = 0.52) or FAT1(p = .006, HR = 0.23) alterations when compared to non-altered subjects in the treatment arm; NOTCH1 alterations showed strong trends in improved PFS. Additionally, high tumor mutational burden (TMB) combined with alterations in the TP53 pathway showed significant OS improvement (p = .052, HR = 0.44) compared with the placebo arm. Conclusions: This analysis highlights unique insights into the mechanism of Buparlisib and Paclitaxel in of metastatic SCCHN patients; a significant improvement in efficacy observed when specific alterations are considered in the context of immune infiltration. These observations will be further explored in the ongoing Phase 3 clinical trial, BURAN. Additional analysis to be presented at the meeting include prognostic and predictive value of each biomarker and combination, differences between tumor and plasma samples, and comparison with end of treatment samples.
B7H3 expression in sarcoma.
Authors: Meghan Maureen Lynch, Farres Obeidin, Borislav A. Alexiev, Eleanor Y. Chen, Pedro Viveiros, Brett Schroeder, Kelly Hudkins, Timothy M. Fan, Mary Weber Redman, Kelsey K. Baker, George Jour, Seth Pollack
Journal: Journal of Clinical Oncology (2023)

e23517 Background: Targeted therapy development in sarcoma has been burdened by the heterogeneity of this rare group of tumors. B7H3 is an immune checkpoint molecule in the same family as PD-L1 (also known as B7H1). Its limited expression in non-cancerous tissues and over-expression in numerous tumor types makes it an attractive target for cancer immunotherapy. Available data suggests high expression of B7H3 in certain sarcoma subtypes, including rhabdomyosarcoma, osteosarcoma, liposarcoma, Ewing sarcoma, synovial sarcoma and chondrosarcoma. This study was conducted to further explore B7H3 expression patterns across sarcoma subtypes and the relationship, if any, with PD-1 and PD-L1 expression. Methods: This single-institution, retrospective analysis evaluated soft tissue sarcoma Formalin-Fixed Paraffin-Embedded tumor specimens in patients with a variety of different subtypes. Specimens were evaluated for expression of B7H3, vessel positivity for B7H3, B7H3 staining pattern, and expression of PD-L1 and PD-1. The association between B7H3 expression and baseline and tumor factors was tested using the Mantel Haenszel test or two-sample T-test. Overall survival was estimated using the Kaplan-Meier method where survival time was calculated from diagnosis to death (or last follow-up for those last known to be alive). Results: 156 sarcoma specimens encompassing 16 subtypes were included. B7H3 was broadly expressed across sarcoma subtypes, with some degree of expression found in 91% of samples and 61% demonstrating high levels of B7H3 expression. All tumor samples expressing B7H3 exhibited the biomarker in at least 80% of tumor cells per sample (with a mean of 92.34% of cells testing positive for B7H3). All samples positive for B7H3 showed both cytoplasmic and membranous expression, and B7H3 vessel positivity was found in 90% (137/152) of samples. There were no significant differences in expression or level of expression when stratified by sarcoma subtype, prior treatment(s), tumor size, tumor grade or patient age. No significant difference in overall survival was seen regardless of B7H3 expression or expression levels across sarcoma subtypes. There was no correlation between B7H3 expression and expression of PD-L1 or PD-1 in tumor cells. Conclusions: This is the most comprehensive analysis of B7H3 expression in sarcoma to date. This data shows high levels of B7H3 expression across sarcoma subtypes, suggesting its feasibility as a therapeutic target for future sarcoma treatments. Future clinical trials are needed to evaluate its numerous actions and if manipulation of B7H3 can be employed to improve outcomes in sarcoma. [Table: see text]
Integrating polygenic risk scores into clinical breast cancer models: Influence on prediction in diverse cohorts.
Authors: George B.J. Busby, Alessandro Bolli, Jen Kintzle, Scott Kulm, John Neary, Paolo Di Domenico, Daniel Morganstern, Giordano Botta
Journal: Journal of Clinical Oncology (2023)

10506 Background: Breast cancer (BC) is the second leading cause of cancer death in women worldwide. Periodic mammography screening has been shown to reduce breast cancer mortality by around 20% in average-risk women and several BC risk models are currently used to identify women at higher risk who can be targeted with increased or earlier screening. However, despite their broad use, these models display only moderate discrimination performance (AUC ranging between 0.51 to 0.68). Here we explore the potential of integrating PRS into a BC risk model using a testing dataset comprising over 175,000 women of diverse ancestry in the UK Biobank and Women Health’s Initiative Cohorts. Methods: We built and validated novel ancestry-specific BC PRSs utilizing novel methodology that leverage multiple Genome Wide Association Studies (GWASs) and linkage disequilibrium maps. We assessed genetic ancestry from 5 continental level ancestry groups across all individuals and applied the PRSs to our testing dataset to assess the clinical implications of integrating genetic information to the Tyrer-Cuzick (TC) breast cancer clinical risk model. Results: The PRSs were well calibrated and displayed high risk stratification (Odds Ratios per Standard Deviation: 1.41 (1.28-1.62) to 1.76 (1.40-2.20; Table) which were comparable or better than benchmarking comparisons with previously published PRS panels. Across genetic ancestries, integrating PRS led to a relative increase of women identified at high lifetime BC risk (20% or higher) from between 1.7 fold (East-Asian ancestry) to around 3 fold (European ancestry). The Net Reclassification Improvement compared to the TC-only model was around 12% for East-Asian (0.001-0.254), European (0.111-0.133), and Admixed American ancestries (0.002-0.228), 17% (0.079-0.266) for South-Asians, and 5% (0.008-0.094) for African ancestry individuals (Table). Conclusions: Our results demonstrate that optimizing PRSs for genetic ancestries and integrating them into BC risk models can lead to a significant improvement in risk stratification. This can enable more targeted use of enhanced screening and prevention strategies improving their cost/benefit ratio.[Table: see text]
Efficacy and safety of elranatamab in patients with high-risk relapsed/refractory multiple myeloma (RRMM): A subgroup analysis from MagnetisMM-3.
Authors: Sarah Marie Larson, Nizar J. Bahlis, Christopher Maisel, Lionel Karlin, Asya Varshavsky Yanovsky, Eric Leip, Sharon T. Sullivan, Andrea Viqueira, Cyrille Touzeau
Journal: Journal of Clinical Oncology (2023)

e20017 Background: Data from the ongoing phase 2 MagnetisMM-3 (NCT04649359) study demonstrated the efficacy and safety of elranatamab in patients (pts) with RRMM and no prior BCMA-directed therapy (Cohort A). Results in high-risk subgroups are reported. Methods: Eligibility criteria, dosing and administration were previously reported (Bahlis, ASH 2022). Subgroups analyzed were R-ISS stage (I/II/III ), cytogenetic abnormalities (standard/high risk [high-risk defined by the presence of t(4;14), t(14;16) or del(17p)]), extramedullary disease (EMD) at baseline (Y/N), bone marrow plasma cell involvement (BMPC) at baseline (&lt;50%/≥50%), and penta-refractory disease (Y/N). Results include data up through ~12 months after last pt initial dose. Results: Median treatment durations and the proportions of pts receiving treatment at the data cut-off are reported in the Table. The most frequent cause of discontinuation was progressive disease which was higher for all high-risk subgroups than the corresponding lower risk subgroups. A clinical benefit, assessed by the objective response rate (ORR), was observed across subgroups (Table). A multivariable logistic regression analysis for ORR including baseline age, ECOG, sex, region, cytogenetic risk, presence of EMD, BMPC involvement, prior stem cell transplant, R-ISS stage, number of prior lines, type of myeloma, and penta-refractory disease showed presence of EMD at baseline and non-IgG myeloma (vs IgG) as predictive of lower ORR. Light chain-only myeloma (vs IgG) was predictive of higher ORR. Median duration of response (DOR) was not reached in subgroups by 12 months, DOR rate at 12 months is reported in the Table. Any grade TEAEs were reported in 100% of pts in the study. The incidence of grade 3/4 TEAEs was overall similar across subgroups (Table). Conclusions: Elranatamab is efficacious and has a manageable safety profile in pts with high-risk RRMM and no prior BCMA-directed therapy. Clinical trial information: NCT04649359 . [Table: see text]
A national survey of current scenario and future perspectives of cancer research in Brazil.
Authors: Heloisa Resende, Taiane Francieli Rebelatto, Gustavo Werutsky, Gustavo Cartaxo de Lima Gössling, Vinícius Aguiar, Guilherme Lopes, Biazi Assis, Lilian Martins Arruda, Carlos H. Barrios
Journal: Journal of Clinical Oncology (2023)

e18721 Background: Epidemiological and clinical cancer research are the backbone to understand tumor behavior and to develop new therapies in oncology. However, several countries including Brazil and many regions in the world have a very small participation in cancer research. Despite 625.000 new cancer cases recorded in Brazil in 2022, only 2,2% of ongoing cancer clinical trials are available in the country We conducted an online survey to describe physician engagement with research and to identify the main barriers precluding participation and conduct of clinical cancer research in the country. Methods: An anonymous online survey of 23 objective questions was sent by e-mail to members of the Latin American Cooperative Oncology Group (LACOG) and the Brazilian Society of Clinical Oncology (SBOC). The first 13 questions addressed demographic information, medical training, and previous research participation. In the second part, the main barriers to engagement and participation in clinical trials in Brazil were addressed. Continuous variables were measured by median and range. Analyses were performed using SAS statistical software (version 9.4; SAS Institute, Inc. Cary, NC). Results: 109 physicians answered the survey. Most participants were oncologists (N = 98, 89.9%), living in capital cities (N = 84, 77.1%), were from the Southeast region of Brazil (N = 63, 57.8%), worked at institutions providing exclusively private healthcare (N = 59, 54.1%). Of the 109 respondents, 83 (76.1%) reported working in research centers (as investigators or sub-investigators). Surprisingly, 31.2% of physicians recognized they invite less than 1% of their patients to participate in clinical trials, even though 98 (89.9%) considered the participation of patients in clinical trials extremely relevant. The main barriers compromising conduct of research in the country were low number of available trials proposed by pharma/Clinical Research Organizations (48.2%) and the lack of qualified human resources to staff research sites (22.9%). Other reported barriers were the lengthy regulatory approval process (42.2%), followed by lack of awareness of clinical research by patients resulting in low recruitment rates (24.1%). Of the 26 (23.8%) respondents not working with research, 25 (96.1%) reported interest in being involved, 31.8% have tried participating in research, and 62.4% reported limited knowledge of trial procedures. Conclusions: These results suggest a clear need to further engage physicians in clinical research activities in Brazil. Patient education strategies should improve the low recruitment rates and secondarily increase the number of proposed trials to the country.
Oncology literacy: Educational book for children, families and health professionals.
Authors: Simone Lehwess Mozzilli, Verônica Andrade, Milena Oliveira, Marina Salvetti
Journal: Journal of Clinical Oncology (2023)

e24208 Background: With the progress of technology, not only the range of treatments and procedures increases, but also the amount of information and the complexity of the language. Appropriate materials are needed especially when stakeholders have different specificities, but need to speak the same language to understand each other and facilitate engagement in treatment. The aim of this study was to evaluate Beabook, an educational book designed for children with cancer, their family members and health professionals. Methods: The educational book, which has more than 150 terms from the oncology environment and is in more than 200 hospitals and institutions in Brazil, was scored using SAM - Suitability Assessment of Materials, a grading scale to evaluate suitability of health information materials based on categories: content, literacy demand, graphics, layout and typography, learning stimulation and motivation, and cultural appropriateness. Results: The book was analyzed by 61 participants, including children (n = 12) undergoing cancer treatment, remission, palliative care and cured, validating with a score of 26 (maximum scale score - 100%), family members (n = 20): mothers, fathers, siblings, uncles, with a score of 25.6 (98.4%) and health professionals (n = 29): doctors, nurses, psychologists, nutritionists, physiotherapists among others, with score of 25.4 (97.6%), resulting in a final score of 25.6 (98.6%), which represents material above expectations, fully adequate. Conclusions: An educational book suitable for different groups with different perspectives is of great importance in an environment where information is often omitted with the intention of protecting children, ludic communication is confused with fanciful stories and professionals do not have support materials to learn to communicate with patients and families. Studies prove that a unified, standardized and adequate language between stakeholders increases engagement and empowerment, being important mainly in the health area, where helping in the diagnosis and treatment does not imply only in the provision of clinical resources but in the guidance and sharing of information that demystify and build new representations.
Impact of pandemic on accrual of minority participants to interventional cancer clinical trials.
Authors: Jaia Wingard, Vicki Sallee, Peter Edward Gabriel, Abigail Doucette, Wallace P Wormley, Colleen M. Grosso, Robert A. Schnoll, Armenta L. Washington, Daniel A Pryma, Katherine Nathanson, Carmen Guerra, Robert H. Vonderheide
Journal: Journal of Clinical Oncology (2023)

e18581 Background: Underrepresentation of Black (BL) and Hispanic (HIS) participants in cancer clinical trials remains a major challenge. Community- and patient-facing initiatives facilitate minority participant accrual (Guerra et al, ASCO, 2021); however, limitations due to COVID-19 pandemic and loss of in-person activities in the community have threatened efforts. In response, the Abramson Cancer Center (ACC) at Penn launched community and patient outreach initiatives that were virtual or socially distanced, including drive-through cancer screening ‘mini-clinics’ in community parking lots, mobile mammography, virtual patient education, and community clinical trial ambassadors. Here, we report accrual of BL and HIS participants to interventional cancer clinical trials at the ACC from 2019 through 2021. Methods: Two geographic areas were examined (i) the ACC 12-county catchment area, where 81% of tumor registry patients reside, and (ii) Philadelphia County, ACC’s physical location and where 22% of ACC patients reside. The primary metrics evaluated per geographic area for BL and HIS individuals were: % of residents in the population, % of cancer cases overall, % of adult cancer patients seen and cared for at the ACC, and % of adult participants enrolled on treatment (T) or non-therapeutic interventional (NTI) trials. Data sources were: US Census 2010 and 2020; state cancer registry data for 2015-2019 (most recent); and ACC data for 2019-2021. Pragmatic clinical trials were excluded. Results: The total new patients seen at ACC decreased by 13% in 2020 compared to 2019 rebounding in 2021. Compared to 2019, total T accruals decreased 40% in 2020 and 45% in 2021. NTI accruals decreased 58% in 2020 but recovered by 2021. Primary metrics are shown in the Table. From 2019 through 2021, the % of BL and HIS patients seen at the ACC was constant. For BL patients from the entire catchment or from Philadelphia County, the % enrolled on T trials matched or exceeded the % of BL patients at ACC. For NTI accruals, there was a modest decrease in 2021 in the % of BL participants for the 12 counties but an increase in Philadelphia. For HIS individuals, the % of patients seen at ACC and enrolled on T or NTI trials was stable. Conclusions: With community- and patient-facing efforts adjusted for pandemic limitations, relative accrual of BL and HIS participants to interventional clinical trials was sustained at our cancer center in the first two years of the COVID-19 pandemic. [Table: see text]